Netropsin interactions in the minor groove of d(GGCCAATTGG) studied by a combination of resolution enhancement and ab initio calculations
Netropsin interactions in the minor groove of d(GGCCAATTGG) studied by a combination of resolution enhancement and ab initio calculations
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DOI：
10.1111/j.1742-4658.2005.04773.x
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发表时间：
2005-07-01
期刊：
影响因子：
5.4
通讯作者：
Van Meervelt, L
中科院分区：
文献类型：
--
作者：
Van Hecke, K;Nam, PC;Van Meervelt, L
通过单晶x射线技术测定了小凹槽粘合剂netropsin与d（GGCCAATTGG）之间的配合物的结构。使用< smallcapitals > refmac 5.1.24对结构进行优化，剩余r因子为20.0%（包括68个水分子）。利用晶体工程和低温冷却技术，可以将分辨率提高到1.75埃，从而可以明确地确定药物的构象和取向。如前文所述，药物的酰胺态氮原子与A和T碱基对的N3和O2原子之间分别形成了分叉的氢键，明确地将结构归类为i类。由于鸟嘌呤上庞大的NH2基团被认为可以防止药物在小凹槽中结合，因此通过从头计算量子化学方法进一步研究了几个酰胺态和胍态末端接触的详细性质。
The structure of the complex between the minor groove binder netropsin and d(GGCCAATTGG) was determined via single-crystal X-ray techniques. The structure was refined to completion using < smallcapitals > refmac 5.1.24, resulting in a residual R-factor of 20.0% (including 68 water molecules). Using crystal engineering and cryocooling techniques, the resolution could be enhanced to 1.75 angstrom, resulting in an unambiguous determination of the drug conformation and orientation. As previously noticed, bifurcated hydrogen bonds are formed between the amide nitrogen atoms of the drug and the N3 and O2 atoms of A and T base pairs, respectively, clearly cataloging the structure to class I. As the bulky NH2 group on guanine was believed to prevent binding of the drug in the minor groove, the detailed nature of several of the amidinium and guanidinium end contacts were further investigated by ab initio quantum chemical methods.